2020 Fiscal Year Final Research Report
Improvement of the surface properties of nanoparticles by using a novel stealth device and their application to nucleic acid carrier controlling tumor microenvironment.
Project/Area Number |
18H03540
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 90120:Biomaterials-related
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Research Institution | Kyoto Pharmaceutical University |
Principal Investigator |
Hama Susumu 京都薬科大学, 薬学部, 講師 (60438041)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Keywords | DDS / 腫瘍微小環境 / 血中滞留性 |
Outline of Final Research Achievements |
Liposomal nucleic acid carrier in response to tumor microenvironment has been developed by the surface modification of a novel blood circulating device TGL. Slightly acidic pH sensitive peptide (SAPSP)-modified liposomes showed pH-sensitivity even when the surface hydrophilicity was increased by modifying TGL on their surface. When plasmid DNA was encapsulated into TGL-modified SAPSP-lipo, the expression of exogenous gene in cancer cells was enhanced in response to slightly acidic pH. In tumor penetration type SAPSP (SAPSP-iRGD)-modified liposomes, the tumor penetration of SAPSP-iRGD-lipo was enhanced by their surface modification of TGL. Furthermore, Akt inhibitor encapsulated into TGL-SAPSP-iRGD-lipo induced cell death at slightly acidic pH. Therefore, TGL is a novel blood circulating device capable of improving the surface properties of nanoparticles without inhibiting the function of tumor microenvironment-responsive drug carrier.
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Free Research Field |
薬物送達学
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Academic Significance and Societal Importance of the Research Achievements |
現在の癌治療ドラッグデリバリーシステムの開発において、癌への受動的送達のために血中滞留性素子のポリエチレングリコール(PEG)をナノ粒子型キャリアーの表面に修飾する必要がある。しかし、PEG修飾はナノ粒子の細胞内取り込みを阻害することが課題である。本研究で開発した新規血中滞留性素子TGLは、ナノ粒子の細胞内取り込みを阻害しないだけでなく、各種機能性ナノ粒子の機能を維持することが可能である。そのため、TGLはPEGに取って代わる新規血中滞留性素子として、広く医薬品開発へ応用されることが期待される。
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